Prediction and validation of exenatide risk marker effects on progression of renal disease: Insights from EXSCEL.

Journal Article (Journal Article)

AIM: To assess whether the previously developed multivariable risk prediction framework (PRE score) could predict the renal effects observed in the EXSCEL cardiovascular outcomes trial using short-term changes in cardio-renal risk markers. MATERIALS AND METHODS: Changes from baseline to 6 months in HbA1c, systolic blood pressure (SBP), body mass index (BMI), haemoglobin, total cholesterol, and new micro- or macroalbuminuria were evaluated. The renal outcomes were defined as a composite of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). Relationships between risk markers and long-term renal outcomes were determined in patients with type 2 diabetes from the ALTITUDE study using multivariable Cox regression analysis, and then applied to short-term changes in risk markers observed in EXSCEL to predict the exenatide-induced impact on renal outcomes. RESULTS: Compared with placebo, mean HbA1c, BMI, SBP and total cholesterol were lower at 6 months with exenatide, as was the incidence of new microalbuminuria. The PRE score predicted a relative risk reduction for the 30% eGFR decline + ESRD endpoint of 11.3% (HR 0.89; 95% CI 0.83-0.94), compared with 12.7% (HR 0.87; 0.77-0.99) observed risk reduction. For the 40% eGFR decline + ESRD endpoint, the predicted and observed risk reductions were 11.0% (HR 0.89; 0.82-0.97) and 13.7% (HR 0.86, 0.72-1.04), respectively. CONCLUSIONS: Integrating short-term risk marker changes into a multivariable risk score predicted the magnitude of renal risk reduction observed in EXSCEL.

Full Text

Duke Authors

Cited Authors

  • Idzerda, NMA; Clegg, LE; Hernandez, AF; Bakris, G; Penland, RC; Boulton, DW; Bethel, MA; Holman, RR; Heerspink, HJL

Published Date

  • May 2020

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 798 - 806

PubMed ID

  • 31912603

Pubmed Central ID

  • PMC7187441

Electronic International Standard Serial Number (EISSN)

  • 1463-1326

Digital Object Identifier (DOI)

  • 10.1111/dom.13958


  • eng

Conference Location

  • England